Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sensing and efficient utilization of environmental nutrients are critical for the survival of microorganisms in environments where nutrients are limited, such as within mammalian hosts. Candida albicans is a common member of the human microbiota as well as an opportunistic fungal pathogen. The amide derivative sugar N-acetlyglucosamine (GlcNAc) is an important signaling molecule for C. albicans that could be a major nutrient source for this fungus in host settings. In this article, we review progress made over the past two decades on GlcNAc utilization, sensing, and functions in C. albicans and its related fungal species. GlcNAc sensing and catabolic pathways have been intensively studied in C. albicans. The C. albicans protein Ngt1 represents the first identified GlcNAc-specific transporter in eukaryotic organisms. In C. albicans, GlcNAc not only induces morphological transitions including the yeast to hyphal transition and the white to opaque phenotypic switch, but it also promotes fungal cell death. The Ras-cAMP/PKA signaling pathway plays critical roles in regulating these processes. Given the importance of GlcNAc sensing and utilization in C. albicans, targeting GlcNAc associated pathways and key pathway components could be promising in the development of new antifungal strategies.
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PMID:N-Acetylglucosamine (GlcNAc) Sensing, Utilization, and Functions in Candida albicans. 3278 32

Mitogen activated protein kinase kinases (MAPKKs) are an important part of evolutionary conserved signaling modules that involved in a variety of cellular processes in response to environmental stimuli. Among them, mitogen-activated protein kinase kinase 2 (MEK2) is the most crucial upstream signaling pathway of ERK1/2 cascade as a therapeutic target for overcoming Ras-driven cancers. However, the mechanisms of MEK2 regulation during tumor progression remain not fully elucidated. Herein, we identified that MEK2 was post-translationally regulated by O-GlcNAcylation. We found that MEK2 associated with OGT and was modified by O-GlcNAc. Mass spectrometry analysis further verified that O-GlcNAcylation of MEK2 occurred at Thr13, which was located in the docking domain (DD) for specifically identifying its target proteins. While total O-GlcNAcylation stimulated the protein stability and phosphorylation of MEK2, Thr13 O-GlcNAcylation of MEK2 specifically enhanced its Thr394 phosphorylation as well as downstream ERK1/2 activation. Genetic ablation of MEK2 O-GlcNAcylation at Thr13 abrogated its ability to promote the proliferation and migration of breast cancer cells. Together, our data demonstrate O-GlcNAcylation of MEK2 might be a key regulatory mechanism during tumorigenesis and is a potential therapeutic target for tumor treatment.
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PMID:O-GlcNAcylation of MEK2 promotes the proliferation and migration of breast cancer cells. 3322 73


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